BACKGROUND: Bipolar disorder (BD) is a complex and heterogeneous psychiatric disorder. It has been suggested that neurodevelopmental factors contribute to the etiology of BD, but a specific neurodevelopmental phenotype (NDP) of the disorder has not been identified. Our objective was to define and characterize an NDP in BD and validate its associations with clinical outcomes, polygenic risk scores, and treatment responses. METHODS: We analyzed the FondaMental Advanced Centers of Expertise for Bipolar Disorders cohort of 4468 patients with BD, a validation cohort of 101 patients with BD, and 2 independent replication datasets of 274 and 89 patients with BD. Using factor analyses, we identified a set of criteria for defining NDP. Next, we developed a scoring system for NDP load and assessed its association with prognosis, neurological soft signs, polygenic risk scores for neurodevelopmental disorders, and responses to treatment using multiple regressions, adjusted for age and gender with bootstrap replications. RESULTS: Our study established an NDP in BD consisting of 9 clinical features: advanced paternal age, advanced maternal age, childhood maltreatment, attention-deficit/hyperactivity disorder, early onset of BD, early onset of substance use disorders, early onset of anxiety disorders, early onset of eating disorders, and specific learning disorders. Patients with higher NDP load showed a worse prognosis and increased neurological soft signs. Notably, these individuals exhibited a poorer response to lithium treatment. Furthermore, a significant positive correlation was observed between NDP load and polygenic risk score for attention-deficit/hyperactivity disorder, suggesting potential overlapping genetic factors or pathophysiological mechanisms between BD and attention-deficit/hyperactivity disorder. CONCLUSIONS: The proposed NDP constitutes a promising clinical tool for patient stratification in BD.
- MeSH
- Bipolar Disorder * genetics MeSH
- Adult MeSH
- Phenotype * MeSH
- Attention Deficit Disorder with Hyperactivity genetics MeSH
- Cohort Studies MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Multifactorial Inheritance genetics MeSH
- Neurodevelopmental Disorders genetics MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Extrapyramídové ochorenia predstavujú heterogénnu skupinu ochorení, v mnohých prípadoch monogénne podmienenú. Najmä zásluhou technologického pokroku v oblasti sekvenovania došlo v posledných rokoch k významnému posunu diagnostických algoritmov pre túto skupinu ochorení, kde sa čoraz viac využívajú metodiky "next-generation sequencing". V prehľadovom článku je prezentovaný súčasný pohľad na genetickú diagnostiku extrapyramídových ochorení, súčasné možnosti testovania a prichádzajúce trendy so zameraním najmä na priblíženie pragmatických algoritmov testovania.
Movement disorders represent a heterogeneous group of diseases, often with a monogenic background. Especially thanks to technological progress in the field of sequencing, there has been a significant shift in diagnostic algorithms for this group of diseases in recent years, where "next-generation sequencing" methodologies are increasingly being used. The review article presents a current view of the genetic diagnostics of movement disorders, current testing options and upcoming trends, with a particular focus on pragmatic testing algorithms.
- MeSH
- Diagnosis, Differential MeSH
- Dystonia diagnosis genetics classification MeSH
- Genetic Testing methods MeSH
- Attention Deficit Disorder with Hyperactivity diagnosis genetics classification MeSH
- Humans MeSH
- Basal Ganglia Diseases * diagnosis genetics classification MeSH
- Parkinsonian Disorders diagnosis genetics classification MeSH
- High-Throughput Nucleotide Sequencing methods MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
ADHD is a common chronic neurodevelopmental disorder and is characterized by persistent inattention, hyperactivity, impulsivity and are often accompanied by learning and memory impairment. Great evidence has shown that learning and memory impairment of ADHD plays an important role in its executive function deficits, which seriously affects the development of academic, cognitive and daily social skills and will cause a serious burden on families and society. With the increasing attention paid to learning and memory impairment in ADHD, relevant research is gradually increasing. In this article, we will present the current research results of learning and memory impairment in ADHD from the following aspects. Firstly, the animal models of ADHD, which display the core symptoms of ADHD as well as with learning and memory impairment. Secondly, the molecular mechanism of has explored, including some neurotransmitters, receptors, RNAs, etc. Thirdly, the susceptibility gene of ADHD related to the learning and impairment in order to have a more comprehensive understanding of the pathogenesis. Key words: Learning and memory, ADHD, Review.
- MeSH
- Attention Deficit Disorder with Hyperactivity * psychology genetics MeSH
- Humans MeSH
- Disease Models, Animal MeSH
- Memory MeSH
- Memory Disorders * psychology etiology MeSH
- Learning Disabilities psychology etiology MeSH
- Learning MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
INTRODUCTION AND METHODS: We report two series of individuals with DDX3X variations, one (48 individuals) from physicians and one (44 individuals) from caregivers. RESULTS: These two series include several symptoms in common, with fairly similar distribution, which suggests that caregivers' data are close to physicians' data. For example, both series identified early childhood symptoms that were not previously described: feeding difficulties, mean walking age, and age at first words. DISCUSSION: Each of the two datasets provides complementary knowledge. We confirmed that symptoms are similar to those in the literature and provides more details on feeding difficulties. Caregivers considered that the symptom attention-deficit/hyperactivity disorder were most worrisome. Both series also reported sleep disturbance. Recently, anxiety has been reported in individuals with DDX3X variants. We strongly suggest that attention-deficit/hyperactivity disorder, anxiety, and sleep disorders need to be treated.
As a prevalent neurodevelopmental disease, attention-deficit hyperactivity disorder (ADHD) impairs the learning and memory capacity, and so far, there has been no available treatment option for long-term efficacy. Alterations in gene regulation and synapse-related proteins influence learning and memory capacity; nevertheless, the regulatory mechanism of synapse-related protein synthesis is still unclear in ADHD. LncRNAs have been found participating in regulating genes in multiple disorders. For instance, lncRNA Metastasis Associated Lung Adenocarcinoma Transcript 1 (MALAT1) has an essential regulatory function in numerous psychiatric diseases. However, how MALAT1 influences synapse-related protein synthesis in ADHD remains largely unknown. Here, our study found that MALAT1 decreased in the hippocampus tissue of spontaneously hypertensive rats (SHRs) compared to the standard controls, Wistar Kyoto (WKY) rats. Subsequent experiments revealed that MALAT1 enhanced the expression of neurexin 1 (NRXN1), which promoted the synapse-related genes (SYN1, PSD95, and GAP43) expression. Then, the bioinformatic analyses predicted that miR-141-3p and miR-200a-3p, microRNAs belonging to miR-200 family and sharing same seed sequence, could interact with MALAT1 and NRXN1 mRNA, which were further confirmed by luciferase report assays. Finally, rescue experiments indicated that MALAT1 influenced the expression of NRXN1 by sponging miR-141-3p/200a-3p. All data verified our hypothesis that MALAT1 regulated synapse-related proteins (SYN1, PSD95, and GAP43) through the MALAT1-miR-141-3p/200a-3p-NRXN1 axis in ADHD. Our research underscored a novel role of MALAT1 in the pathogenesis of impaired learning and memory capacity in ADHD and may shed more light on developing diagnostic biomarkers and more effective therapeutic interventions for individuals with ADHD.
The human dopamine transporter gene SLC6A3 has been consistently implicated in several neuropsychiatric diseases but the disease mechanism remains elusive. In this risk synthesis, we have concluded that SLC6A3 represents an increasingly recognized risk with a growing number of familial mutants associated with neuropsychiatric and neurological disorders. At least five loci were related to common and severe diseases including alcohol use disorder (high activity variant), attention-deficit/hyperactivity disorder (low activity variant), autism (familial proteins with mutated networking) and movement disorders (both regulatory variants and familial mutations). Association signals depended on genetic markers used as well as ethnicity examined. Strong haplotype selection and gene-wide epistases support multimarker assessment of functional variations and phenotype associations. Inclusion of its promoter region's functional markers such as DNPi (rs67175440) and 5'VNTR (rs70957367) may help delineate condensate-based risk action, testing a locus-pathway-phenotype hypothesis for one gene-multidisease etiology.
1. elektronické vydání 1 online zdroj (128 stran)
Kniha nabízí ucelený pohled na problematiku variability ADHD v dětském věku i dospělosti. Analyzuje problematiku od etiologie, přes neurobiologické a somatické příčiny, variabilitu v odpovědi na léčbu, až po psychologické a sociální souvislosti. Přehled variability ADHD využijí odborníci v oblastech nejen psychiatrie a medicíny obecně, ale i psychologie, pedagogiky a všech souvisejících oblastí. Text zahrnuje také výsledky vybraných původních studií autorů a jako první v české odborné literatuře přináší kompletní diagnostická kritéria ADHD dle DSM-5 v oficiálním českém překladu. V přílohách jsou uvedeny metody pro hodnocení ADHD symptomatologie v dětství i v dospělosti.; Kniha nabízí ucelený pohled na problematiku variability ADHD v dětském věku i dospělosti.Analyzuje problematiku od etiologie, přes neurobiologické a somatické příčiny, variabilitu v odpovědi na léčbu, až po psychologické a sociální souvislosti. Přehled variability ADHD využijí odborníci v oblastech nejen psychiatrie a medicíny obecně, ale i psychologie, pedagogiky a všech souvisejících oblastí. Text zahrnuje také výsledky vybraných původních studií autorů a jako první v české odborné literatuře přináší kompletní diagnostická kritéria ADHD dle DSM-5 v oficiálním českém překladu. V přílohách jsou uvedeny metody pro hodnocení ADHD symptomatologie v dětství i v dospělosti.
Attention deficit/hyperactivity disorder (ADHD) is one of the most commonly diagnosed developmental disorders in childhood characterized by hyperactivity, impulsivity and inattention. ADHD manifests in the child's development by deficits in cognitive, executive and perceptor-motor functions, emotional regulation and social adaptation. Although the exact cause has not yet been known, the crucial role in the development of this disease plays the interaction of genetic, neurobiological and epigenetic factors. According to current knowledge, ADHD is defined as a biological dysfunction of central nervous system with genetically or organically defined deficits in noradrenergic and dopaminergic neurotransmission associated with structural abnormalities, especially in prefronto-striatal regions. In this context, a significant part of the difficulties could be due to a faulty control of fronto-striato-thalamo-cortical circuits important for attention, arousal and executive functions. Moreover, ADHD is associated with abnormal autonomic regulation. Specifically, reduced cardiac-linked parasympathetic activity associated with relative sympathetic dominance indexed by low heart rate variability can represent a noninvasive marker for prefrontal hypoactivity. However, the mechanisms underlying altered autonomic regulation in ADHD are still unknown. In this aspect, the evaluation of central autonomic regulation by noninvasive methods, namely pupillometry and eye-tracking, may provide novel information for better understanding of the neurobiological pathomechanisms leading to ADHD.
- MeSH
- Autonomic Nervous System physiopathology MeSH
- Attention Deficit Disorder with Hyperactivity diagnosis genetics physiopathology MeSH
- Humans MeSH
- Brain physiopathology MeSH
- Eye Movements physiology MeSH
- Attention physiology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
Vydání první 127 stran : ilustrace, tabulky ; 23 cm
Kniha nabízí ucelený pohled na problematiku variability ADHD v dětském věku i dospělosti. Nakladatelská anotace. Kráceno; Kniha nabízí ucelený pohled na problematiku variability ADHD v dětském věku i dospělosti.Analyzuje problematiku od etiologie, přes neurobiologické a somatické příčiny, variabilitu v odpovědi na léčbu, až po psychologické a sociální souvislosti. Přehled variability ADHD využijí odborníci v oblastech nejen psychiatrie a medicíny obecně, ale i psychologie, pedagogiky a všech souvisejících oblastí. Text zahrnuje také výsledky vybraných původních studií autorů a jako první v české odborné literatuře přináší kompletní diagnostická kritéria ADHD dle DSM-5 v oficiálním českém překladu. V přílohách jsou uvedeny metody pro hodnocení ADHD symptomatologie v dětství i v dospělosti.
- MeSH
- Psychology, Child MeSH
- Attention Deficit Disorder with Hyperactivity etiology genetics therapy MeSH
- Biological Variation, Individual MeSH
- Psychology, Developmental MeSH
- Conspectus
- Psychiatrie
- NML Fields
- psychiatrie
- NML Publication type
- kolektivní monografie
Biologické aspekty etiologie ADHD a poruch chování, včetně jejich souvislostí s užívanou farmakoterapií, představují, vedle faktorů prostředí a problémů v meziosobní interakci v rodině, základ pochopení etiopatogeneze uvedených poruch a poruch příbuzných (např. tiková porucha, obsedantně kompulzivní porucha u dětí). Uvedené poznatky o neurovývojových poruchách dokládají výrazné pokroky ve znalostech příčin onemocnění, v jejich léčbě a tím také v možnostech prevence.
Next to environmental factors and problems with interpersonal interaction in family represent developmental findings the basic of understanding these disorders (ADHD, conduct disorders, obsessive-compulsive disorders, tic disorders etc.). Knowledges of neurodevelopment disorders represent new possibilities of prevention and treatment.
- MeSH
- Antihypertensive Agents MeSH
- Antipsychotic Agents MeSH
- Aripiprazole administration & dosage therapeutic use MeSH
- Atomoxetine Hydrochloride administration & dosage therapeutic use MeSH
- Clonidine administration & dosage contraindications therapeutic use MeSH
- Child MeSH
- Dopamine beta-Hydroxylase physiology MeSH
- Adult MeSH
- Mental Disorders * diagnosis genetics therapy MeSH
- Attention Deficit Disorder with Hyperactivity * diagnosis drug therapy genetics MeSH
- Adrenergic Uptake Inhibitors MeSH
- Humans MeSH
- Methylphenidate administration & dosage therapeutic use MeSH
- Neurobiology MeSH
- Polymorphism, Genetic MeSH
- Primary Prevention MeSH
- Prognosis MeSH
- Receptors, Dopamine D2 physiology genetics MeSH
- Receptors, Dopamine D4 physiology genetics MeSH
- Risperidone administration & dosage therapeutic use MeSH
- Wakefulness-Promoting Agents therapeutic use MeSH
- Central Nervous System Stimulants MeSH
- Check Tag
- Child MeSH
- Adult MeSH
- Humans MeSH
- Publication type
- Review MeSH
